Research Topics

B Cell Activation

Following maturation in the bone marrow and spleen, immunocompetent B cells remain in peripheral tissues until they encounter an antigen and are activated. B cell activation requires two distinct signals, and results in B cell differentiation into memory B cells or plasma cells. The first activation signal occurs upon antigen binding to B cell receptors (BCRs). Upon binding to the BCR, the antigen is internalized by receptor-mediated endocytosis, digested, and complexed with MHC II molecules on the B cell surface. The second activation signal occurs via either a thymus-dependent or a thymus-independent mechanism. Most B cell responses to antigen require the interaction of B cells with T helper cells (thymus-dependent activation). Presentation of an antigen-class II MHC complex on a B cell enables it to act as an antigen-presenting cell (APC) to T cells. T cell receptors (TCR) on T helper cells bind to the antigen-complexed class II MHC molecule on the B cell surface resulting in T cell activation. The activated T cell then provides a second activation signal to the B cell, which can occur through a variety of proteins. Alternatively, there are a few types of antigens that can directly provide the second B cell activation signal (thymus-independent activation). These antigens include components of some bacterial cell wall components (e.g., lipopolysaccharide) or antigens containing highly repetitious molecules (e.g., bacterial flagellin).

Upon activation, B cells proliferate and form germinal centers where they differentiate into memory B cells or plasma cells. Following differentiation into plasma cells, additional signals initiate plasma cell antibody class switching and regulate antibody secretion. The primary function of plasma cells is the secretion of B cell clone-specific antibodies. Each plasma cell secretes antibodies containing a clonally-unique antigen-binding region joined to a constant immunoglobulin (Ig) isotype-defining region.

B Cell Receptor-Associated Proteins

Thymus-Dependent B Cell Activation

Thymus-Independent B Cell Activation

Other Proteins Involved in Regulating B Cell Activation

Regulators of Plasma Cell Activity